Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

OBJECTIVES: The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. DESIGN: Observational cohort study. SETTING: Neurocritical care unit, Cambridge, United Kingdom. PATIENTS: Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. CONCLUSIONS: Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.

The lower limit of reactivity as a potential individualised cerebral perfusion pressure target in traumatic brain injury: a CENTER-TBI high-resolution sub-study analysis.

BACKGROUND: A previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort. METHODS: Recordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal-Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong's test. RESULTS: Average LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p = < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP. CONCLUSIONS: Using a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury.

Loop gain response to increased cerebral blood flow at high altitude.

PURPOSE: To compare loop gain (LG) before and during pharmacological increases in cerebral blood flow (CBF) at high altitude (HA). Loop gain (LG) describes stability of a negative-feedback control system; defining the magnitude of response to a disturbance, such as hyperpnea to an apnea in periodic breathing (PB). "Controller-gain" sensitivity from afferent peripheral (PCR) and central-chemoreceptors (CCR) plays a key role in perpetuating PB. Changes in CBF may have a critical role via effects on central chemo-sensitivity during sleep. METHODS: Polysomnography (PSG) was performed on volunteers after administration of I.V. Acetazolamide (ACZ-10mg/kg) + Dobutamine (DOB-2-5 µg/kg/min) to increase CBF (via Duplex-ultrasound). Central sleep apnea (CSA) was measured from NREM sleep. The duty ratio (DR) was calculated as ventilatory duration (s) divided by cycle duration (s) (hyperpnea/hyperpnea + apnea), LG = 2π/(2πDR-sin2πDR). RESULTS: A total of 11 volunteers were studied. Compared to placebo-control, ACZ/DOB showed a significant increase in the DR (0.79 ± 0.21 vs 0.52 ± 0.03, P = 0.002) and reduction in LG (1.90 ± 0.23 vs 1.29 ± 0.35, P = 0.0004). ACZ/DOB increased cardiac output (CO) (8.19 ± 2.06 vs 6.58 ± 1.56L/min, P = 0.02) and CBF (718 ± 120 vs 526 ± 110ml/min, P < 0.001). There was no significant change in arterial blood gases, minute ventilation (VE), or hypoxic ventilatory response (HVR). However, there was a reduction of hypercapnic ventilatory response (HCVR) by 29% (5.9 ± 2.7 vs 4.2 ± 2.8 L/min, P = 0.1). CONCLUSION: Pharmacological elevation in CBF significantly reduced LG and severity of CSA. We speculate the effect was on HCVR "controller gain," rather than "plant gain," because PaCO2 and VE were unchanged. An effect via reduced circulation time is unlikely, as the respiratory-cycle length did not change.

Return to Activity After Arthroscopically Assisted Triangular Fibrocartilage Complex Repair: A Systematic Review.

OBJECTIVE: To evaluate patients' ability to return to preinjury activity level after arthroscopically assisted triangular fibrocartilage complex (TFCC) repair. DATA SOURCES: The PubMed electronic library was systematically searched from inception to August 2021 for any eligible articles using a combination of the phrases "TFCC," "return to sport," "return to work," and "athlete." RESULTS: Studies that evaluated patients who had undergone arthroscopic repair of isolated TFCC injury and reported objective or patient-reported outcome measures were included. Fifteen studies representing 478 patients fulfilled the inclusion criteria. An average of 84% of patients were able to fully return to their previous work or sport activities. Most studies reported that range of motion (ROM) and grip strength (GS) both returned to >90% of the contralateral side, and every study that evaluated pain levels found a significant reduction in pain postoperatively. Mayo Modified Wrist Score was reported as excellent or good in 83% of patients, and the average Disabilities of the Arm, Shoulder, and Hand score was 13.8 postoperatively. CONCLUSION: Patients were able to return to their previous work or sport activities at a high rate after TFCC repair, even those participating in more strenuous activities. Measurable functional outcomes of ROM and GS were also reliably restored to near preinjury levels. Patient-reported outcomes of pain and disability were similarly improved after TFCC repair. Current literature has established the long-term success of TFCC repair but is lacking in evaluation of the time points at which patients can expect functional status to be restored.

Early cardiac dysfunction in obese adolescents with Down syndrome or autism.

BACKGROUND: Obesity in adolescents with intellectual and developmental disabilities) occurs at twice the frequency as their typically developing peers. Typically developing adolescents with obesity have abnormal cardiac function (as measured by strain echocardiography) and cardiac mass, but the effects of obesity on cardiac health in adolescents with Down syndrome or autism spectrum disorder are unknown. The purpose of this study was to evaluate the impact of body mass index on cardiac function in adolescents with Down syndrome or autism. METHODS: Adolescents (age 12-21 years) with Down syndrome (n = 28), autism (n = 33), and age-/sex-matched typically developing controls (n = 15) received an echocardiogram optimised for strain analysis at a single timepoint. Measures of ventricular function, mass, and size were collected. Regression modelling evaluated the impact of body mass index and intellectual and developmental disabilities diagnosis on these cardiac measures. RESULTS: In regression modelling, an elevated body mass index z-score was associated with diminished systolic biventricular function by global strain (left ventricular longitudinal strain ß 0.87, P < 0.001; left ventricular circumferential strain ß 0.57, p 0.003; right ventricular longitudinal strain ß 0.63, P < 0.001). Diminished left ventricular diastolic function by early diastolic strain rate was also associated with elevated body mass index (global longitudinal end-diastolic strain rate ß -0.7, P < 0.001). No association was found between traditional (non-strain) measures of systolic and diastolic ventricular function and body mass index z-score. CONCLUSIONS: Obesity in adolescents with Down syndrome or autism negatively impacts cardiac function as measured by echocardiographic strain analysis that was not detected by traditional parameters.

A prospective observational study on the effect of emboli exposure on cerebral autoregulation in cardiac surgery requiring cardiopulmonary bypass.

OBJECTIVE: Cerebrovascular autoregulation impairment has been associated with stroke risk in cardiac surgery. We hypothesized that greater arterial emboli exposure in open-chamber surgery might promote dysautoreguation. METHODS: Forty patients underwent closed or open-chamber surgery. Transcranial Doppler detected emboli and measured bilateral middle cerebral artery flow velocities. Cerebral autoregulation was assessed by averaging the mean velocity index ("Mx," a continuous moving correlation between cerebral blood flow velocity and mean arterial pressure) over 30 min before and after aortic cross-clamp removal. RESULTS: Median (interquartile range) emboli counts were 775 (415, 1211) and 2664 (793, 3734) in the closed-chamber and open-chamber groups. Most appeared after the removal of the aortic cross-clamp (open-chamber 1631 (606, 2296)), (closed-chamber 229 (142, 384)), with emphasis on the right hemisphere (open-chamber: 826 (371, 1622)), (closed-chamber 181 (66, 276)). Linear mixed model analyses of mean velocity index change showed no significant overall effect of group (0.08, 95% CI: -0.04, 0.21; p = 0.19) or side (0.01, 95% CI: -0.03, 0.05; p = 0.74). There was an interaction between group and side (p = 0.001), manifesting as a greater increase in mean velocity index in the right hemisphere in the open than the closed group (mean difference: 0.15, 95% CI: 0.02, 0.27; p = 0.03). CONCLUSIONS: Overall, change in mean velocity index before and after cross-clamp removal did not differ between groups. However, most emboli entered the right cerebral hemisphere where this change was significantly greater in the open-chamber group, suggesting a possible association between embolic exposure and dysautoregulation.

Interviews with parents of adolescents with intellectual and developmental disabilities in a weight management study.

BACKGROUND: Adolescents and young adults with intellectual and developmental disabilities are at risk of obesity. Parents influence their diet and physical activity behaviours and therefore, can play important roles in weight management. The aims of this qualitative study were to explore parents' experiences assisting their son or daughter to participate in a weight management study. METHODS: Interviews were completed at 6 months with 27 parents whose adolescent or young adult had completed the weight loss portion of an 18-month weight management study. Interviews were recorded, transcribed and thematic analysis performed. RESULTS: Parents shared insights about how well program components worked with their family, and what strategies worked best to adopt healthier dietary choices and become more physically active. The importance of meeting regularly with someone outside the family to encourage healthier habits was stressed. CONCLUSIONS: Future weight management studies should involve parents and their adolescents to help tailor strategies and adapt intervention approaches.

Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.

Twenty-five years ago, a new physiological preparation called the working heart-brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advantages and disadvantages along with potential future applications, and provide photographs and technical drawings of all the customised equipment used for the preparation. Using mice or rats, the WHBP is an in situ experimental model that is perfused via an extracorporeal circuit benefitting from unprecedented surgical access, mechanical stability of the brain for whole cell recording and an uncompromised use of pharmacological agents akin to in vitro approaches. The preparation has revealed novel mechanistic insights into, for example, the generation of distinct respiratory rhythms, the neurogenesis of sympathetic activity, coupling between respiration and the heart and circulation, hypothalamic and spinal control mechanisms, and peripheral and central chemoreceptor mechanisms. Insights have been gleaned into diseases such as hypertension, heart failure and sleep apnoea. Findings from the in situ preparation have been ratified in conscious in vivo animals and when tested have translated to humans. We conclude by discussing potential future applications of the WHBP including two-photon imaging of peripheral and central nervous systems and adoption of pharmacogenetic tools that will improve our understanding of physiological mechanisms and reveal novel mechanisms that may guide new treatment strategies for cardiorespiratory diseases.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

The impact of exercise and cumulative physical activity on energy intake and diet quality in adults enrolled in the Midwest Exercise Trial for the Prevention of Weight Regain.

The purpose of this study was to assess impact of different volumes of exercise as well as cumulative moderate to vigorous physical activity (MVPA) on energy intake (EI) and diet quality, as assessed by the Healthy Eating Index-2010(HEI-2010), across a 12-month weight maintenance intervention. Participants were asked to attend group behavioural sessions, eat a diet designed for weight maintenance and exercise either 150, 225 or 300 min/week. Dietary intake was assessed by 3-d food records, and MVPA was assessed by accelerometry. Two hundred and twenty-four participants (42·5 years of age, 82 % female) provided valid dietary data for at least one time point. There was no evidence of group differences in EI, total HEI-2010 score or any of the HEI-2010 component scores (all P > 0·05). After adjusting for age, sex, time, group and group-by-time interactions, there was an effect of cumulative MVPA on EI (1·08, P = 0·04), total HEI-2010 scores (-0·02, P = 0·003), Na (-0·006, P = 0·002) and empty energy scores (-0·007, P = 0·004. There was evidence of a small relationship between cumulative daily EI and weight (ß: 0·00187, 95 % CI 0·001, P = 0·003). However, there was no evidence for a relationship between HEI total score (ß: -0·006, 95 % CI 0·07, 0·06) or component scores (all P > 0·05) and change in weight across time. The results of this study suggest that increased cumulative MVPA is associated with clinically insignificant increases in EI and decreases in HEI.

Comparison of different metrics of cerebral autoregulation in association with major morbidity and mortality after cardiac surgery.

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery. METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. Regression models were used to examine associations of area under curve and duration of mean arterial pressure below thresholds with stroke, acute kidney injury (AKI), and major morbidity and mortality. RESULTS: Both mean flow index and cerebral oximetry index identified the cerebral lower limit of autoregulation below which MAP was associated with a higher incidence of AKI and major morbidity and mortality. Based on magnitude and significance of the estimates in adjusted models, the area under curve of MAP < lower limit of autoregulation had the strongest association with AKI and major morbidity and mortality. The odds ratio for area under the curve of MAP < lower limit of autoregulation was 1.05 (95% confidence interval, 1.01-1.09), meaning every 1 mm Hg h increase of area under the curve was associated with an average increase in the odds of AKI by 5%. CONCLUSIONS: For cardiac surgery patients, area under curve of MAP < lower limit of autoregulation using mean flow index or cerebral oximetry index had the strongest association with AKI and major morbidity and mortality. Trials are necessary to evaluate this target for MAP management.

Pro-Con Debate: The Clinical (Ir)relevance of the Lower Limit of Cerebral Autoregulation for Anesthesiologists.

In this Pro-Con commentary article, we discuss whether the lower limit of cerebral autoregulation is clinically relevant for anesthesiologists. The central question regarding this issue is whether mean arterial blood pressure below the lower limit of autoregulation is detrimental for the brain. The Pro side argues that continuous monitoring of cerebral autoregulation has revealed an association between going below the lower limit and mortality in the critically ill patient. Conversely, the Con side argues that cerebral autoregulation is only one of various defense mechanisms of the brain that protect against cerebral hypoperfusion, and that cerebral autoregulation may be more important to protect against intracranial hypertension.

A prospective observational study of emboli exposure in open versus closed chamber cardiac surgery.

OBJECTIVE: Exposure to cerebral emboli is ubiquitous and may be harmful in cardiac surgery utilizing cardiopulmonary bypass. This was a prospective observational study aiming to compare emboli exposure in closed-chamber with open-chamber cardiac surgery, distinguish particulate from gaseous emboli and examine cerebral laterality in distribution. METHODS: Forty patients underwent either closed-chamber procedures (n = 20) or open-chamber procedures (n = 20). Emboli (gaseous and solid) were detected using transcranial Doppler in both middle cerebral arteries in two monitoring phases: 1, initiation of bypass to the removal of the aortic cross-clamp; and 2, removal of aortic cross-clamp to 20 minutes after venous decannulation. RESULTS: Total (median (interquartile range)) emboli counts (both phases) were 898 (499-1366) and 2617 (1007-5847) in closed-chamber and open-chamber surgeries, respectively. The vast majority were gaseous; median 794 (closed-chamber surgery) and 2240 (open-chamber surgery). When normalized for duration, there was no difference between emboli exposures in closed-chamber and open-chamber surgery in phase 1: 6.8 (3.6-15.2) versus 6.4 (2.0-18.1) emboli per minute, respectively. In phase 2, closed-chamber surgery cases were exposed to markedly fewer emboli than open-chamber surgery cases: 9.6 (5.1-14.9) versus 43.3 (19.7-60.3) emboli per minute, respectively. More emboli (total) passed into the right cerebral circulation: 985 (397-2422) right versus 376 (198-769) left. CONCLUSIONS: Patients undergoing open-chamber surgery are exposed to considerably higher numbers of cerebral arterial emboli after removal of the aortic cross-clamp than those undergoing closed-chamber surgery, and more emboli enter the right middle cerebral artery than the left. These results may help inform the evaluation of the pathophysiological impact of emboli exposure.

Influence of the mode of heating on cerebral blood flow, non-invasive intracranial pressure and thermal tolerance in humans.

KEY POINTS: The human brain is particularly vulnerable to heat stress; this manifests as impaired cognition, orthostatic tolerance, work capacity and eventually, brain death. The brain's limitation in the heat is often ascribed to inadequate cerebral blood flow (CBF), but elevated intracranial pressure is commonly observed in mammalian models of heat stroke and can on its own cause functional impairment. The CBF response to incremental heat strain was dependent on the mode of heating, decreasing by 30% when exposed passively to hot, humid air (sauna), while remaining unchanged or increasing with passive hot-water immersion (spa) and exercising in a hot environment. Non-invasive intracranial pressure estimates (nICP) were increased universally by 18% at volitional thermal tolerance across all modes of heat stress, and therefore may play a contributing role in eliciting thermal tolerance. The sauna, more so than the spa or exercise, poses a greater challenge to the brain under mild to severe heating due to lower blood flow but similarly increased nICP. ABSTRACT: The human brain is particularly vulnerable to heat stress; this manifests as impaired cognitive function, orthostatic tolerance, work capacity, and eventually, brain death. This vulnerability is often ascribed to inadequate cerebral blood flow (CBF); however, elevated intracranial pressure (ICP) is also observed in mammalian models of heat stroke. We investigated the changes in CBF with incremental heat strain under three fundamentally different modes of heating, and assessed whether heating per se increased ICP. Fourteen fit participants (seven female) were heated to thermal tolerance or 40°C core temperature (Tc ; oesophageal) via passive hot-water immersion (spa), passive hot, humid air exposure (sauna), cycling exercise, and cycling exercise with CO2 inhalation to prevent heat-induced hypocapnia. CBF was measured with duplex ultrasound at each 0.5°C increment in Tc and ICP was estimated non-invasively (nICP) from optic nerve sheath diameter at thermal tolerance. At thermal tolerance, CBF was decreased by 30% in the sauna (P < 0.001), but was unchanged in the spa or with exercise (P ≥ 0.140). CBF increased by 17% when end-tidal PCO2 was clamped at eupnoeic pressure (P < 0.001). On the contrary, nICP increased universally by 18% with all modes of heating (P < 0.001). The maximum Tc was achieved with passive heating, and preventing hypocapnia during exercise did not improve exercise or thermal tolerance (P ≥ 0.146). Therefore, the regulation of CBF is dramatically different depending on the mode and dose of heating, whereas nICP responses are not. The sauna, more so than the spa or exercise, poses a greater challenge to the brain under equivalent heat strain.

The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia.

Hemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signaling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: 1) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic hemodilution (n = 10, aged 29 ± 7 yr); 2) at altitude (6 ± 2 days acclimatization at 5,050 m), before and during hypervolumic hemodilution (n = 11, aged 27 ± 5 yr) with room air and additional hypoxia [fraction of inspired oxygen ([Formula: see text])= 0.15]; and 3) at altitude (4,340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n = 6, aged 39 ± 17 yr), before and during isovolumic hemodilution with room air and hyperoxia (end-tidal Po2 = 100 mmHg). At sea level, hemodilution mildly increased pulmonary artery systolic pressure (PASP; +1.6 ± 1.5 mmHg, P = 0.01) and pulmonary vascular resistance (PVR; +0.7 ± 0.8 wu, P = 0.04). In contrast, after acclimation to 5,050 m, hemodilution did not significantly alter PASP (22.7 ± 5.2 vs. 24.5 ± 5.2 mmHg, P = 0.14) or PVR (2.2 ± 0.9 vs. 2.3 ± 1.2 wu, P = 0.77), although both remained sensitive to additional acute hypoxia. In Andeans with EE at 4,340 m, hemodilution lowered PVR in room air (2.9 ± 0.9 vs. 2.3 ± 0.8 wu, P = 0.03), but PASP remained unchanged (31.3 ± 6.7 vs. 30.9 ± 6.9 mmHg, P = 0.80) due to an increase in cardiac output. Collectively, our series of studies reveal that HPV is modified by the duration of exposure and the prevailing hematocrit level. In application, these findings emphasize the importance of accounting for hematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.NEW & NOTEWORTHY Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

Visualization of Intracranial Pressure Insults After Severe Traumatic Brain Injury: Influence of Individualized Limits of Reactivity.

Cerebral perfusion pressure (CPP) lower limits of reactivity can be determined almost continuously after severe traumatic brain injury (TBI), and deviation below the lower limit carries important prognostic information. In this study, we used a recently derived coloured contour method for visualizing intracranial pressure (ICP) insults to describe the influence of having a CPP above the CPP lower limits of reactivity after severe TBI. In a cohort of 729 patients, we examined the relationship between ICP insults and the 6-month Glasgow Outcome Scale score, using colour-coded plots, as described previously. We then assessed this relationship when ICP insults were above or below the CPP lower limit of reactivity. We found a curvilinear relationship whereby even prolonged durations of low-intensity ICP insults were not associated with poor outcomes but short durations of high-intensity insults were. When only ICP insults with a CPP below the CPP lower limit of reactivity were considered, a much lower intensity of ICP insults could be tolerated. A CPP above the lower limits of reactivity exerts a protective effect, whereas a CPP below the lower reactivity limits renders the patient vulnerable to increased morbidity from intracranial hypertension.

Analysis of the Association Between Lung Function and Brain Tissue Oxygen Tension in Severe Traumatic Brain Injury.

INTRODUCTION: Low brain tissue oxygen tension (PbtO2) has been shown to be an independent factor associated with unfavourable outcomes in traumatic brain injury (TBI). Although PbtO2 provides clinicians with an understanding of ischaemic and non-ischaemic derangements of brain physiology, the value alone can be the result of several factors, including partial arterial oxygenation pressure (PaO2), haemoglobin levels (Hb) and cerebral perfusion pressure (CPP). METHODS: This chapter presents a single-centre, retrospective cohort study of 70 adult patients with severe TBI who were admitted to the Neurocritical Care Unit (NCCU) at Addenbrooke's Hospital (Cambridge, UK) between October 2014 and December 2017. A total of 303 simultaneous measurements of different variables that included (but were not limited to) intracranial pressure (ICP), PaO2, PbtO2, CPP and the fraction of inspired oxygen (FiO2) were considered in this work. We conducted a correlation analysis between all of the variables. We also implemented a longitudinal data analysis of the PbtO2 and PaO2/FiO2 ratio (PF ratio). RESULTS: There were strong and independent correlations between PbtO2 and the PF ratio, and between PbtO2 and PaO2, with adjusted p values of <0.001 for both correlations. After adjustment for ICP, age, sex and the Glasgow Coma Scale (GCS) score, a PF ≤ 330 was shown to be an independent risk factor for a compromised PbtO2 value of <20, with an adjusted odds ratio of 1.94 (95% confidence interval 1.12-3.34) and a p value of 0.02. CONCLUSION: Brain and lung interactions in patients with TBI patients have complex interrelationships. Our results confirm the importance of employing lung-protective strategies to prevent brain hypoxia in patients with TBI.

Cerebrovascular Consequences of Elevated Intracranial Pressure After Traumatic Brain Injury.

We compared various descriptors of cerebral hemodynamics in 517 patients with traumatic brain injury (TBI) who had, on average, elevated (>23 mmHg) or normal (<15 mmHg) intracranial pressure (ICP). In a subsample of 193 of those patients, transcranial Doppler ultrasound (TCD) recordings were made. Arterial blood pressure (ABP), cerebral blood flow velocity (CBFV), cerebral autoregulation indices based on TCD (the mean flow index (Mx; the coefficient of correlation between the the cerebral perfusion pressure CPP and flow velocity) and the autoregulation index (ARI)), and the pressure reactivity index (PRx) were compared between groups. We also analyzed the TCD-based cerebral blood flow (CBF) index (diastolic CBFV/mean CBFV), the spectral pulsatility index (sPI), and the critical closing pressure (CrCP). Finally, we also looked at brain tissue oxygenation (cerebral oxygen partial tension (PbtO2)) in 109 patients. The mean cerebral perfusion pressure (CPP) was lower in the group with elevated ICP (p < 0.01), despite a higher mean arterial pressure (MAP) (p < 0.005) and worse autoregulation (as assessed with the Mx, ARI, and PRx indices), greater CrCP, a lower CBF index, and a higher sPI (all with p values of <0.001). Neither the mean CBFV nor PbtO2 reached significant differences between groups. Mortality in the group with elevated ICP was almost three times greater than that in the group with normal ICP (45% versus 17%). Elevated ICP affects cerebral autoregulation. When autoregulation is not working properly, the brain is exposed to ischemic insults whenever CPP falls.

Variability of the Optic Nerve Sheath Diameter on the Basis of Sex and Age in a Cohort of Healthy Volunteers.

Many studies have demonstrated that the optic nerve sheath diameter (ONSD) is a good indicator of intracranial pressure (ICP). There are uncertainties regarding the optimal ONSD threshold, considering age and sex differences in the healthy population, and these differences could lead to uncertainties in evaluation of ONSD in pathological conditions.The aim of this prospective observational study was to investigate if age and sex could influence ONSD in a cohort of healthy Italian volunteers recruited during preanesthetic assessment for low-risk surgical procedures.The population was stratified for sex (males versus females) and for age (18-44 years, 45-64 years, and ≥65 years). The axial and longitudinal ONSD diameters were measured by two trained investigators.A significant difference in ONSD between males and females was found (median 4.2 (interquartile range 3.9-4.6) versus 4.1 (interquartile range 3.6-4.2) mm, P = 0.01), and a positive correlation between ONSD and age was found (R = 0.50, P < 0.0001).It was concluded that ONSD increases with age and is significantly larger in the healthy male population. These discrepancies should be taken into consideration when ONSD measurement is performed.

Lower Limit of Reactivity Assessed with PRx in an Experimental Setting.

In traumatic brain injury, longer time spent with a cerebral perfusion pressure (CPP) below the pressure reactivity index (PRx)-derived lower limit of reactivity (LLR) has been shown to be statistically associated with higher mortality. We set out to scrutinise the behaviour of LLR and the methods of its estimation in individual cases by performing retrospective analysis of intracranial pressure (ICP), arterial blood pressure (ABP) and laser Doppler flow (LDF) signals recorded in nine piglets undergoing controlled, terminal hypotension. We focused on the sections of the recordings with stable experimental conditions where a clear breakpoint of LDF/CPP characteristic (LLA) could be identified.In eight of the nine experiments, when CPP underwent a monotonous decrease, the relationship PRx/CPP showed two breakpoints (1 - when PRx starts to rise; 2 - when PRx saturates at PRx > 0.3), with LDF-based LLA sitting between them. LLR (CPP at PRx reaching 0.3 in the error bar chart) was close to the lower LLR breakpoint.In conclusion, when CPP has a monotonous decrease, PRx starts worsening before CPP crosses the LLA. A further decrease in CPP below LLA would cause a decrease in CBF, even if the pressure reactivity is not completely lost. This pattern should be taken into account when PRx is used to detect LLA continuously.